A misleading patient in intensive care.
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Biomedical subjects
Publications and source records attributed to J Kennedy.
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Investigation of the post-PKS biosynthetic steps to the cholesterol-lowering agent lovastatin (1) using an Aspergillus terreus strain with a disrupted lovC gene, which is essential for formation of 4a,5-dihydromonacolin L (3), shows that 7 and 3 are precursors to 1, and demonstrates that lovastatin diketide synthase (lovF protein) does not require lovC.
Genes influence the development of anxiety disorders, but the specific loci involved are not known. Genetic association studies of anxiety disorders are complicated by the complexity of the phenotypes and the difficulty in identifying appropriate candidate loci. We have begun to examine the genetics of behavioral inhibition to the unfamiliar (BI), a heritable temperamental predisposition that is a developmental and familial risk factor for panic and phobic disorders. Specific loci associated with homologous phenotypes in mouse models provide compelling candidate genes for human BI. We conducted family-based association analyses of BI using four genes derived from genetic studies of mouse models with features of behavioral inhibition. The sample included families of 72 children classified as inhibited by structured behavioral assessments. We observed modest evidence of association (P = 0.05) between BI and the glutamic acid decarboxylase gene (65 kDA isoform), which encodes an enzyme involved in GABA synthesis. No significant evidence of association was observed for the genes encoding the adenosine A(1A) receptor, the adenosine A(2A) receptor, or preproenkephalin. This study illustrates the potential utility of using candidate genes derived from mouse models to dissect the genetic basis of BI, a possible intermediate phenotype for panic and phobic disorders.
OBJECTIVES: To assess the risks for adult-onset acute leukemia associated with employment in the New Zealand meat industry. METHODS: A total of 110 incident leukemia cases identified from referrals to one of six treatment centers between 1989 and 1991 were compared with 199 general population controls. Detailed occupational exposure histories were obtained by interview. RESULTS: There was an elevated risk associated with ever having worked in an abattoir (OR = 2.3, 95% CI 1.0-5.2), which appeared confined to those with over 2 years exposure (OR = 4.9, 95% CI 1.5-15.6). The excess risk was confined to abattoir workers having direct contact with animals or animal products (OR = 5.2 95% CI 1.2-22.2). Ever having worked as a butcher was associated with elevated risk (OR = 2.9, 95% CI 1.1-7.2), confined to those individuals who worked as a butcher in an abattoir (OR = 4.8) or who butchered livestock on farms (OR = 8.2). No increased risk was found for work as a retail/wholesale butcher or meatpacker (OR = 1.2). CONCLUSIONS: This study found increased leukemia risks associated with employment in the meat industry. These were confined to abattoir workers with over 2 years employment in the industry, and to persons whose jobs involved contact with animals or animal tissue, implying that biological exposures may be responsible.
OBJECTIVES: To assess the risks for adult-onset acute leukemia associated with electrical employment in New Zealand. METHODS: The occupational and environmental exposures histories of 110 incident leukemia cases and 199 general population controls were compared. The cases were recruited through referrals to treatment centers in New Zealand between 1989 and 1991. For subjects classified as having worked in one or more of the "electrical occupations," the degree of exposures to extremely low frequency electromagnetic fields (ELF-EMFs) was assessed in detail using a job-exposure matrix. RESULTS: An odds ratio of 1.9 (95% Cl 1.0-3.8) was found for subjects who had ever worked in an electrical occupation. Significantly increased risks for leukemia are seen amongst welders/flame cutters (OR = 2.8 (95% CI 1.2-6.8)) and telephone line workers (OR = 5.81 (95% CI 1.2-27.8)). The excess leukemia risk appeared to be confined to acute non-lymphocytic leukemia (OR=2.31 (95% CI 1.2-4.6)), in comparison to acute lymphoblastic leukemia (OR = 0.9 (95% CI 0.3-2.9)) but for the latter category the numbers were very small. A dose-response effect was also found, with acute leukemia risk rising with increasing occupational magnetic field exposure, based on both current and historical occupational field exposure estimates. CONCLUSIONS: The findings of the current study indicate a significantly elevated risk of acute leukemia for electrical workers overall, and for the specific occupational categories of welders/flame cutters and telephone line workers. A dose-response effect was also found, indicating that acute leukemia risk was related to historical and current magnetic field exposures in an occupational context.
BACKGROUND: The histological diagnosis of early lesions of mycosis fungoides (MF) is often difficult for dermatopathologists and prior studies have shown a low agreement rate among pathologists. An important reason for such difficulty may be the lack of specific histological criteria. METHODS: We tested a new method to interpret and report biopsies suspicious for MF. The method is based on a grading system reflecting the pathologist's degree of diagnostic certainty. A panel of four pathologists independently assessed a set of 50 biopsies suspicious for MF first without (Phase I) and subsequently with specific histological criteria (Phase II). A third Phase was carried out after a training session, using a new set of cases with corresponding immunophenotyping and gene rearrangement analysis. Weighted and unweighted kappa statistics were used to assess inter- and intra-pathologist variation. RESULTS: The consensus rate among pathologists improved from 48% in Phase I to 76% in Phase III. Overall precision weighted kappas increased from 0.630 in Phase I to 0.854 in Phase III, indicating excellent inter-pathologist agreement by Phase III. There was a significant association between the presence of an abnormal phenotype and/or T-cell clonality and a higher diagnostic score. CONCLUSIONS: The use of uniform criteria and training sessions can substantially improve the consensus rate among pathologists in the diagnosis of MF.
BACKGROUND: A growing body of evidence suggests that idiopathic environmental intolerance (IEI) is a psychophysiologic disorder with prominent features of anxiety/panic and somatization, although proponents of a toxicogenic explanation claim, despite a lack of convincing evidence, that symptoms arise from exposure to otherwise nonnoxious environmental agents. Patient behaviour is characterized by strenuous avoidance of perceived triggers to the point of severe impairment of normal social and vocational functioning. IEI proponents claim that previous studies showing a high prevalence of psychopathology in patients with IEI and studies showing panic responses to known panicogenic challenges merely reflect the anxiety-producing result of living with IEI. OBJECTIVE: We explored whether IEI and panic disorder, personality traits, or both shared an underlying neurogenetic basis that would predate the anxiety of IEI symptomatology. The DNA of patients with IEI was examined for the presence of known panic disorder-associated cholecystokinin B (CCK-B) receptor alleles and for personality trait-associated dopamine D4 receptor polymorphisms. METHODS: Eleven patients with typical IEI symptoms were recruited and were individually matched to normal control subjects from an existing bank for age, sex, and ethnic background. Genomic DNA was extracted from peripheral blood samples. CCK-B and dopamine D4 receptor polymorphisms were examined by using standard PCR-based techniques. RESULTS: There was a significantly higher prevalence of the panic disorder-associated CCK-B receptor allele 7 in subjects with IEI (9/22 [40.9%]) compared with control subjects (2/22 [9.1%], P =.037). There was no difference in personality trait-associated polymorphisms of the gene encoding dopamine D4 receptor between patients and control subjects. CONCLUSIONS: These findings provide preliminary evidence that IEI and panic disorder share a common neurogenetic basis, which would predate the anxiety-producing effects of IEI symptoms. Further studies with larger samples are warranted, but these results support previous studies that suggest that panic disorder may account for much of the symptomatology in at least some cases of IEI and provide a basis for rational treatment strategies.
BACKGROUND: Accurate assessments of need for disability assistance are essential for effective planning of disability support services, but there is little national data on type and acuity of need. OBJECTIVE: To more fully delineate the type and magnitude of disability assistance needs across the US population, focusing on factors associated with perceived gaps in assistance. RESEARCH DESIGN: Secondary analysis of national household survey. SUBJECTS: Twenty-five thousand eight hundred five adults identified as disabled in the 1994 and 1995 National Health Interview Surveys. MEASURES: Self-reported assistance deficits with activities of daily living (ADLs) and instrumental activities of daily living (IADLs). RESULTS: An estimated 3.2 million adults with disabilities have at least one assistance deficit, usually involving IADLs like housework. However, approximately 970 thousand adults report one or more assistance deficits with basic ADLs. Compared to adults with met ADL needs, people with ADL assistance deficits are more likely to live alone, to be in poor health, to be a member of a racial or ethnic minority, and to need help with multiple activities. DISCUSSION: These analyses suggest a relatively high rate of unmet and undermet need for disability assistance in the general population. However, only a small number of these adults report assistance deficits with basic ADLs. This group is a logical target for expanded state or federal personal assistance services programming.
OBJECTIVE: As in other English-speaking countries, asthma is a major and increasing health problem in New Zealand. This study examined the risk factors for asthma in children aged 7-9. METHODS: Cases and controls were randomly selected from participants in the Wellington arm of the International Study of Asthma and Allergies in Childhood (ISAAC). Cases were children with a previous diagnosis of asthma and current medication use (n=233), and controls were children with no history of wheezing and no diagnosis of asthma (n=241). RESULTS: After controlling for confounders, factors significantly associated with asthma were maternal (OR=3.36, 95% CI 1.88-5.99) and paternal asthma (OR-2.67, 95% CI 1.42-5.02), and male sex (OR=1.81, 95% CI 1.17-2.81). Children from social classes 5 and 6 or with unemployed parents (OR=2.32, 95% CI 1.22-4.44) were significantly more likely to have asthma than children in social classes 1 and 2. There was no significant association between having polio vaccination (OR=2.48, 95% CI 0.83-7.41), hepatitis B vaccination (OR=0.66, 95% CI 0.42-1.04) or measles/mumps/rubella vaccination (OR=1.43, 95% CI 0.85-2.41) and asthma. CONCLUSIONS: This study has confirmed the associations of family history and lower socio-economic status with current asthma in 7-9 year old children. The role of vaccinations requires further research.
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This paper documents the resilience of medical and nursing profession-based subcultures and the extent of the differences between them. Against this background, we assess the capacity and willingness of medical and nursing managers to promote changes that will extend the accountability of clinicians and engender more evidence-based, financially driven and output-oriented approaches to service delivery.
Data from the 1994 and 1995 Disability Supplements of the National Health Interview Survey (NHIS) were used to estimate rates of utilization of vocational services and examine employment outcomes for adults with disabilities who have received vocational services. Those living outside the formal long-term care system, and who were self or proxy identified as having mental retardation, were compared with other adults with disabilities. Analyses suggest that compared to other working-age persons with disabilities, adults with mental retardation (a) have a different population profile, (b) receive different types of services, (c) experience similar levels of satisfaction, (d) have much lower rates of competitive employment, and (e) are much more likely to be employed in segregated work settings. Research and policy implications of findings are discussed.
OBJECTIVE: Hypoglycemia is a common acute complication of diabetes therapy. The GlucoWatch biographer provides frequent and automatic glucose measurements with an adjustable low-glucose alarm. We have analyzed the performance of the biographer low-glucose alarm relative to hypoglycemia as defined by blood glucose < or = 3.9 mmol/l. RESEARCH DESIGN AND METHODS: The analysis was based on 1,091 biographer uses from four clinical trials. which generated 14,487 paired (biographer and blood glucose) readings. RESULTS: The results show that as the low-glucose alert level of the biographer is increased, the number of true positive alerts (alarm sounds and blood glucose < or = 3.9 mmol/l) and false positive alerts (alarm sounds but blood glucose >3.9 mmol/l) increased. When analyzed as a function of varying low-glucose alert levels, the results show receiver operator characteristic curves consistent with a highly useful diagnostic tool. Setting the alert level from 1.1 to 1.7 mmol/l above the level of concern is likely to optimize the trade-off between true positives and false positives for each user. When the same blood glucose data are analyzed for typical monitoring practices (two or four measurements per day), the results show that fewer hypoglycemic events are detected than those detected with the biographer.
The unique findings from the HOPE (Heart Outcomes Prevention Evaluation) study strongly support extending the use of the angiotensin-converting enzyme (ACE) inhibitor ramipril as a preventive agent for patients at high risk of cardiovascular events with normal left ventricular function. In addition, ramipril provides significant benefit in diabetic patients. These findings will impact on how ramipril is used in primary care, where ACE inhibitors are currently underprescribed. Patients reflecting the inclusion criteria of the HOPE study should be considered as suitable candidates for long-term ramipril therapy as an addition to their existing drug regimen. Screening should include control of kidney function (by serum creatinine), particularly within the first two weeks of treatment, in addition to regular monitoring of serum potassium. However, the HOPE study shows that ramipril is well tolerated at high doses and over a long treatment period. The effectiveness of therapy should also be regularly reviewed and dose adjustments made where necessary. If concern remains, referral to a specialist--a cardiologist or a diabetologist--may ultimately be necessary.
INTRODUCTION: This is a survey to identify what clinical coding systems are currently in use across the European Union, and the states seeking membership to it. We sought to identify what systems are currently used and to what extent they were subject to local adaptation. BACKGROUND: Clinical coding should facilitate identifying key medical events in a computerised medical record, and aggregating information across groups of records. The emerging new driver is as the enabler of the life-long computerised medical record. A prerequisite for this level of functionality is the transfer of information between different computer systems. This transfer can be facilitated either by working on the interoperability problems between disparate systems or by harmonising the underlying data. This paper examines the extent to which the latter has occurred across Europe. METHOD: Literature and Internet search. Requests for information via electronic mail to pan-European mailing lists of health informatics professionals. RESULTS: Coding systems are now a de facto part of health information systems across Europe. There are relatively few coding systems in existence across Europe. ICD9 and ICD 10, ICPC and Read were the most established. However the local adaptation of these classification systems either on a by country or by computer software manufacturer basis; significantly reduces the ability for the meaning coded with patients computer records to be easily transferred from one medical record system to another. CONCLUSIONS: There is no longer any debate as to whether a coding or classification system should be used. Convergence of different classifications systems should be encouraged. Countries and computer manufacturers within the EU should be encouraged to stop making local modifications to coding and classification systems, as this practice risks significantly slowing progress towards easy transfer of records between computer systems.
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